Lecture Notes: Drugs Affecting Cardiovascular and Hematological Systems

Cardiac Cycle Overview

Systole: Ventricles contract, increasing pressure, causing mitral and tricuspid valves to shut, and aortic and pulmonic valves to open, enabling blood ejection into the aorta and pulmonary artery.
Diastole: Ventricles relax, allowing mitral and tricuspid valves to open and blood to flow into the atria. Atrial contraction happens at the end of diastole, pushing blood into ventricles.
Blood Flow: Deoxygenated blood returns to the right atrium via vena cava, moves to right ventricle, then to lungs via pulmonary artery. Oxygenated blood returns to left atrium via pulmonary veins and moves to left ventricle, then ejected to the body via aorta.

Stroke Volume: Amount of blood leaving left ventricle per contraction (~75 ml).
Preload: Passive stretching of ventricular muscle by blood volume at end of diastole, affected by venous return, atrial contractility, and blood left in ventricle.
Contractility: Ventricular squeezing force influenced by muscle health (e.g., myocardial infarction can decrease contractility).
Afterload: Resistance left ventricle must overcome to eject blood, influenced by vessel diameter.

Volume of blood leaving left ventricle per minute (Stroke Volume x Heart Rate).
Compensatory mechanisms in heart failure increase heart rate if stroke volume is low.

Heart Failure: Inability to pump sufficient blood, leading to fluid retention, increased preload and afterload, decreased cardiac output.
Sympathetic Nervous System Activation: Chronic activation in heart failure leads to myocardial hypertrophy.
Renin-Angiotensin-Aldosterone System (RAS): Decreased cardiac output releases renin, activating RAS, causing vasoconstriction and sodium retention.

ACE Inhibitors & ARBs: Interrupt RAS, reduce fluid retention and vasoconstriction.
Beta Blockers: Reduce oxygen demand and workload of the heart.
Calcium Channel Blockers: Used to decrease contraction force.
Digoxin: Cardiac glycoside increasing force of contraction but with high risk.
Diuretics: Reduce fluid overload.

Inhibits angiotensin converting enzyme, reducing angiotensin II, leading to vasodilation and reduced aldosterone secretion.
Increases cardiac output without increasing heart rate.
Adverse effects include hyperkalemia, cough, and serious effects like angioedema.

Non-Selective (e.g., Propranolol): Affects both beta-1 (heart) and beta-2 (lungs) receptors, causing decreased heart rate and force of contraction but risk of respiratory issues.
Selective (e.g., Metoprolol): Primarily affects beta-1, reducing heart rate and force without significant lung effects.

Positive Inotropic Effect: Increases force of contraction.
Narrow Therapeutic Window: Monitoring required to avoid toxicity, which can cause cardiac arrhythmias and non-cardiac symptoms like GI upset and visual changes.

Nesiratide: Vasodilator used in critical care settings to decrease cardiac preload and afterload.
Entresto: Angiotensin receptor neprilysin inhibitor, used in chronic heart failure to modulate natriuretic system and reduce RAS activity.

Monitor electrolyte levels and kidney function when prescribing these medications due to risks of imbalances and toxicity.
Patient education is critical for adherence and recognizing adverse effects, such as signs of electrolyte imbalances and toxicity symptoms.